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THE JOHNS HOPKINS HOSPITAL REPORTS 
MONOGRAPHS. NEW SERIES No. VIII. 



LEUKAEMIA OF THE FOWL: 

SPONTANEOUS AND 

EXPERIMENTAL 



BY 



HARRY C. SCHMEISSER, M. D. 

(From the Department of Pathology of The Johns Hopkins University) 
Illustrated : 4 Plates 



BALTIMORE 

THE JOHNS HOPKINS PRESS 

1915 

[Copyright, 1915, by The Johns Hopkins Press] 



^ftrjsfripfi 



4 






CONTENTS. 

PAGE 

I. Review of the Literature 1 

II. Studies on the Normal Fowl 9 

1. External Appearance 9 

2. Blood 9 

3. Autopsy Protocol (gross) 11 

4. Microscopical Examination 13 

III. A Case of Spontaneous Leukaemia 15 

1. Blood 15 

2. Autopsy Protocol (gross) 16 

3. Microscopical Examination 17 

4. Summary 19 

5. Conclusion 20 

IV. Experimental Leukaemia 20 

1. Preparation of Material, Methods of Injection, etc 20 

2. Clinical History 21 

3. The Blood 22 

4. Autopsy Findings (gross and microscopical) 24 

5. Table: Weights of Body, Organs and Relation of Organs to 

Body at Autopsy 30 

6. Summary 30 

7. Conclusion 31 

V. Conclusion 31 



LEUKEMIA OF THE FOWL: SPONTANEOUS AND 
EXPEEIMENTAL. * f 

By HARRY C. SCHMEISSER, M. D. 

(From the Department of Pathology of The Johns Hopkins University.) 

I. Eeview of the Litekature. 

The first publication was made by Moore ' in 1895-1896, in wliich 
he reported observations upon an epizootic disease of fowls which he 
designated "infectious leukemia." His studies were based upon cases 
obtained from five different outbreaks, and upon those artificially 
produced by means of the specific organism (Bacterium sanguinarium) 
isolated from the organs of these fowls. The descriptions of the 
spontaneous and experimental cases clearly show that he was not 
dealing with a true leuksemia of the fowl, but rather with an acute 
infectious disease, characterized by fever, diminution in the number 
of red blood cells, and increase in number of white blood cells, this 
increase being " restricted " to the polymorphonuclear leucocyte with 
the eosin staining spindles, i. e., the phagocyte of the normal fowl's 
blood. 

Butterfield,' in 1905, reported three cases of aleukasmic lymph- 
adenoid tumors of the hen. His studies were limited to the livers 
of these animals. They correspond in every detail, both grossly and 
microscopically; were uniformly and strikingly enlarged (340, 420, 
270 gm. respectively) and of a diffuse, light, cream, yellow color. 
Histologically, the liver tissue was extensively replaced by large oval 
or round, sometimes irregular, collections of cells. The intralobular 
capillaries were filled with the usual nucleated red blood cells. Most 
of the nodules of tumor cells were thought to be in connection 
with the portal spaces. The cells resembled in general the "large 

* Submitted for publication, October, 1914. 

f Dissertation submitted to the Board of University Studies of The Johns 
Hopkins University, in conformity with the requirements for tlie Degree of 
Doctor of Philosophy, 1914. 



2 Harry C. Schmeisser. 

lymphocyte " of the hen's blood. * Allowing for flattening due to 
pressure, these cells were round or oval, with round or oval nuclei, 
mostly eccentric. The nuclear chromatin appeared granular or 
reticular. The nucleus was not infrequently pale and vesicular with 
one or more bright chromatin bodies. The cytoplasm was present as 
a narrow rim, non-granular, and basophilic. Mitoses were common. 
Between these cells was seen a delicate reticulum. In association with 
these tumor masses were quite large collections of eosinophilic cells, 
the majority showing a single, pale, round or oval, eccentric nucleus 
and a relatively abundant cytoplasm, filled with large, round, elongated, 
or spindle-shaped oxyphilic structures. They varied greatly in size 
and shape. The lymphocytes and eosinophiles were occasionally 
seen in the capillaries, but there was " certainly no definite increase 
within the blood-vessels." From the character of the cells, their rela- 
tion to the portal spaces and absence of the lymphgemia, the condi- 
tion was regarded by Butterfield as a proliferation of periportal 
lymphadenoid tissue, and thought by him to merit the designation 
" aleukaemic lymphadenoma." 

Mohler had under observation five similar cases showing lymphsemia 
and the same lymphadenoid condition. Mohler's description of two 
of his cases, as presented by Butterfield, is as follows : The process 
showed a tendency to involve several organs. In one case the liver 
and spleen were the principal seats, the lungs and intestine were 
also involved. The liver was enlarged to twice the normal size, of 
very light color and mottled. Throughout its surface and within 
its parenchyma were whitish lymphomatous deposits of varying 
diameters. A section shows the liver tissue only partly obliterated 
as a result of a filling up of the interacinous capillaries with leucocytes. 
The spleen was about the size of an ordinary blue plum. Each lung 
contained a white spherical area, the size of a pea and composed 
of hyperplastic lymphoid tissue, infiltrating white cells. In the wall 
of the large intestine, involving the lymphadenoid tissue, were round, 
slightly raised nodules. In the second case the changes were most 
marked in the kidney and spleen. The liver, intestine and heart 
were also involved. The kidneys were three or four times the normal 
size and had macroscopically very much the same appearance as the 
liver in the first case. The myocardium contained some small, whitish 

* Obviously the large mononuclear cell of the classification presented in 
this paper. 



r 



DEC 28 1915 

'GI.A418249 



Leukcemia of the Fowl. 3 

areas. Butterfield, in comparing the histological findings in Mohler's 
cases with his own, finds a convincing similarity between, or identity 
of, the infiltrating cells. In Mohler's cases, the infiltration was more 
diffuse and not so regularly arranged about the portal tissue. Above 
all, the white blood cells were markedly increased in all the blood- 
vessels, from the intraacinar capillaries to the largest veins. The 
predominating white cell was indistinguishable from the cells in the 
tumor masses of both these and Butterfield's cases. From the fore- 
going, Butterfield felt justified in granting " the existence of a 
leukgemic and aleukaemic lymphadenoid hyperplasia in hens." 

Butterfield and Mohler deserve the credit of showing that leukaemia 
occurs in the fowl. Their studies were limited to post-mortem 
findings. 

To Warthin,^ in 1907, we are indebted for the first complete study 
of this disease in fowls. He had the good fortune to secure a living 
animal, which he kept under observation for two and a half months 
before it died. During this time he had an opportunity of care- 
fully studying the clinical course. The blood showed a great reduction 
in the total number of red blood cells. These varied greatly in 
size and shape, and contained less haemoglobin than normal. The 
total number of white cells was greatly increased. Differential counts 
showed a striking increase of the " large lymphocyte " at the ex- 
pense of the other cells of the normal blood. Numerous mononuclear 
forms of the eosinophiles, cells abnormal to the blood, were seen. 
From the blood changes Warthin felt justified in making a diagnosis 
of "lymphatic leukaemia of the large cell type." A careful autopsy 
revealed the following findings: The liver was greatly increased 
in size and was pale yellow in color. The spleen and kidneys were 
also enlarged; both showed numerous yellowish spots from pin- 
point to pin-head in size. In the hjemolymph nodes small yellowish 
nodules were found. The bone-marrow appeared as solid plugs, red- 
dish-yellow and friable. The tissue changes were summarized as 
follows: (1) Tumor-like nodules and infiltrations of lymphoid cells 
in all the organs, particularly in the liver, spleen, kidneys, bone- 
marrow and haemolymph nodes ; (2) replacement of the normal white 
cells of the blood by cells of the large lymphocyte type, more or less 
atypical in character, but identical with cells in the tumor masses. 
From the findings, both in the blood and in the tissue, Warthin made 
the diagnosis of leukaemic lymphocytoma. 



4 Harry C. Schmeisser. 

He likewise examined the material from two additional cases of 
lymphadenoid tumors of the fowl. One proved to be of the aleuksemic 
type, as described by Butterfield ; the other was of the leuksemic form, 
as described above. The histological picture, apart from the increase 
of white cells in the blood-vessels in the one case, was identical in 
both cases and also with that in the cases given above (Butterfield's, 
Mohler's and Warthin's). From these cases Warthin concludes, there- 
fore, that there occurs in the common fowl a condition of disseminated 
lymphocytoma, sometimes aleukaemic, at other times associated with 
an increase of the white cells of the blood, this increase consisting in 
the appearance of great numbers of cells of the large lymphocyte type 
and apparently identical with the lymphoid cells of the tumor nodules. 
He also regards the aleukasmic and leuksemic conditions as genetically 
related, if not actually one and the same process in difEerent stages. 
Both conditions, he thinks, are in all respects analogous to the similar 
ones existing in man. 

The preceding cases appear to be very similar to those reported by 
later investigators and designated by them as splenomedullary in 
type. 

Kon* in 1907, after the appearance of Warthin's article, reported 
what he considers a true case of leuksemic disease of the chicken. 
The gross and microscopical changes, which were studied and reported 
in great detail, are in general identical with those of the cases above. 
In addition, he found giant cells, though only a few, in the bone- 
marrow, and mitoses in the basophiles as well as in the eosinophiles 
in the kidneys. Because of the lack of smears, he determined the 
ratio W/E and made differential counts from sectioned blood-vessels 
of the liver. He found that the white cells, as compared with the 
reds, were greatly increased and that the large mononuclear was the 
predominating cell of the whites. Mitoses of this cell were observed. 
The evidence given, he thinks, is sufficient to consider this a case of true 
leukaemia. Because of the enormous swelling of the spleen and the 
plentiful occurrence of the characteristic cell in the pulp of the normal 
spleen and to a lesser degree in the normal bone-marrow, and in the 
absence of lymphatic swelling and the occurrence of this cell in the nor- 
mal lymph tissue, it seems to him most likely that this is a case of true 
" splenic leukaemia." 

Soshestrenski,' in May, 1908, reported a case of spontaneous 
leukemia of the fowl, xery similar to the case described by Kon. 



Leukcemia of the Fowl. 5 

His study was limited to gross and microscopical findings at autopsy. 
The bone-marrow was omitted. The contents of the blood-vessels 
of the organs were found to be leukaemic. He designates the case 
also as " splenic leukgemia," but in so doing he calls attention to the 
fact that the process involves many of the other organs and appears 
to be only primary and most marked in the spleen. There was 
no enlargement of the lymph-glands. 

With Ellermann and Bang/'' in 1908, the subject takes on a 
different phase. Up to this time, the communications dealt entirely 
with the recording of spontaneous cases of leukemia in the fowl. 
Ellermann and Bang were the first to successfully transmit the 
disease by experimental inoculations from a spontaneous case to 
other, healthy, fowls. In fact, they claim to have been the first to 
successfully produce the disease experimentally in any animal. They 
report the findings in two typical spontaneous cases giving identical 
pictures. The blood study during life was found to be practically 
the same as that of Warthin's case, with the exception that the large 
mononuclears frequently contained in their cytoplasm many granules, 
and thus represented cells which are not found in the normal blood — 
myelocytes. Small granules alternated with very large ones. The 
autopsy showed an enlarged spleen and liver, the latter with white 
dots and streaks. The bone-marrow was gray-red. The other organs 
presented nothing of interest. The microscopical changes were very 
similar to those of Warthin's case. The experimental leukaemia they 
transmitted to the third generation, producing a blood picture and 
organic findings identical with those of the spontaneous cases. 

Pseudoleukaemia, which is characterized by the same organic lesions 
as are found in true leukaemia, but in which the blood picture is 
normal, they found to occur spontaneously among chickens. They 
received from the same flock, at the same time, a leukaemic and 
pseudoleukaemic animal. From the pseudoleukaemic animal, by inocu- 
lation, they produced a leukaemic animal, and conclude, therefore, 
that the leukaemia and pseudoleukaemia of chickens are etiologically 
identical. 

Multiple sarcomatosis of the peritoneum occurs epidemically in the 
fowl. They consider this a manifestation of leukaemia, because by 
inoculation from such a case they produced an atypical leukaemia and 
carried this to the second generation. 

They were successful in two out of five inoculations with a filtrate 
from an emulsion passed through a " Kerze aus Infusorierde " and 



6 Harry C. Schmeisser. 

conclude, therefore, that a cell-free filtrate is ejffective and that the 
cause must be an organized virus. 

In the same year, Ellermann and Bang * reported that the blood of 
leuksemic fowls contained the virus. They also showed that among 
transmitted cases the disease may appear as a typical leukaemia or as 
a pseudoleukaemia, or only as an anaemia with changes in the bone- 
marrow. The injection of five animals with a Berkefeld filtrate re- 
sulted in one early leukaemia. The injected fowls were isolated and 
great care was exercised during the experiment. 

The following year, 1909, Ellermann and Bang," reported the 
transmission of the disease into the sixth generation, and also an addi- 
tional positive Berkefeld filtrate series. Because the disease can be 
produced by a cell-free filtrate, they conclude: (a) Leukemia must 
be an infectious disease; (b) it is to be placed among the diseases due 
to a filterable virus. They call attention to the fact that mitoses in 
the blood are pathological and always present in leukaemia. 

Schriddle," in 1909, was the first to question whether, in leukaemia, 
we are really dealing with an infectious etiology. Basing his con- 
clusions upon experimental work, he claims that chickens, injected 
with extracts of entirely normal organs, present the same changes 
as Ellermann and Bang have reported for leukaemia. He thinks that 
their findings are not leukaemic and that, therefore, there is no proof 
in favor of the infectious etiology of this disease. 

Hirschfeld and Jacoby^' in 1909, report a spontaneous case of 
leukaemia showing changes in the blood and organs which, they claim, 
agree entirely with the description of Ellermann and Bang. In a 
second case, the blood picture, although not typical, appeared to 
them leukaemic. At autopsy this fowl showed a typical chicken tuber- 
culosis. They succeeded in transmitting this tuberculosis, in asso- 
ciation with the apparently leukaemic blood picture, into the fourth 
generation. They did not know whether they were dealing with 
a combination of tuberculosis and leukaemia in the same animal, or 
with pure tuberculosis. An animal injected with a pure culture of 
the chicken tubercle bacillus developed a blood picture identical with 
that of the second spontaneous case. Therefore it seems highly prob- 
able that this case may have been one of pure tuberculosis. At any 
rate, it cannot be accepted as a definite and pure case of leukaemia. 

The following year (1910) the same authors" report the injection 
of fowls subcutaneously from their first spontaneous case. They 



Leukcemia of the Fowl. 7 

obtained no takes and their strain died out. From a leukaemic animal 
given to them by Ellermann and Bang, they transmitted the disease 
into the fifth generation, obtaining both leukaemic and pseudoleukgemic 
cases. In the blood, they found normoblasts and megaloblasts, i. e. 
small and large, round, nucleated, mostly polychromatophilic red blood 
cells. Although they state that the disease begins in the bone- 
marrow, they leave it an open question whether in the chicken one 
is dealing with a myeloid or a lymphoid leukaemia. 

Burckhardt," in 1910, advanced the theory, based upon investiga- 
tions of his own on transmissible chicken leukaemia, that a particular 
leukaemic virus does not exist, and that in the so-called chicken 
leukaemia one is very probably dealing with a very chronic chicken 
tuberculosis. As proof, he claims that with a pure culture from such 
an animal (leukaemic) and also with older pure cultures of chicken 
tubercle bacilli, one can produce the same blood picture described by 
Ellermann and Bang for chicken leukaemia. The anatomical findings, 
he states, likewise correspond. Gratz " suggested that possibly in 
the culture of chicken tubercle bacilli from the leukaemic animal, there 
may have been cultivated, in addition to the tubercle virus, also the 
virus of leukaemia. Friedberger" considered this objection invalid, 
because, as he claimed, one could produce the leukaemic blood picture 
also by using old laboratory tubercle cultures. 

Burckhardt," in 1912, still adheres to his theory, but admits that 
he is unable ever to bring the blood into a leukaemic condition by 
inoculating with tubercle bacilli. 

Hirschfeld and Jacoby" in the same year inform us that they 
presented to Burckhardt and Friedberger the chicken with which 
these investigators started their transmissions, and that on the day 
of delivery it showed a pronounced leuksemic blood picture. The 
animal, in addition, surely had tuberculosis, because all the transmitted 
leukaemic animals of the stock from which this animal originated 
had tuberculosis. They feel confident that in Burckhardt and Fried- 
berger's stock the tuberculosis had crowded out the leukaemia, until 
finally only tuberculous and not leukaemic animals were obtained. They 
had a similar experience with the stock from which Burckhardt and 
Friedberger's animal originated. 

Against the existence of an etiological relationship between tuber- 
culosis and leukaemia, they present the following arguments : (1) The 
blood picture in tuberculosis is never to be confused with that of 



8 Harry C. Schmeisser. 

leuksemia. It is characterized by a hyperleucocytosis due to the 
polymorphs. (Ellermann and Bang" had also stated this fact at an 
earlier date.) (2) The organs of the tuberculous chickens were entirely 
free from the changes which Ellermann and Bang, and they themselves, 
found to be characteristic of leukaemia and which correspond entirely 
with leukaemic lesions in man. (3) By injections of organic emulsions 
obtained from spontaneous tuberculous chickens, or of pure cultures 
of chicken tubercle bacilli, they uniformly produced a typical tuber- 
culous blood picture and organic changes, always without any signs 
of leukgemia. 

Ellermann^*" in 1913 and 1914, in answer to the question whether 
this chicken disease is really leukaemia, shows that it has all the 
symptoms of human leukaemia. He meets Schridde's objection by the 
argument that this investigator's claim was limited to the blood picture, 
and in the absence of the characteristic organic changes, of which he 
makes no mention, his experiments are of no importance. The in- 
jection of an organic emulsion Ellermann never found to cause any 
change in the blood, provided the material was not virulent. Ellermann 
and Bang had previously produced the disease with Berkefeld filtrates 
in three different experiments. In this paper Ellermann reports two 
more successful series. All other investigators have had only negative 
results. Thus, Hirschf eld and Jacoby " were unsuccessful in two experi- 
ments and Burckhardt " in one. 

Ellermann is convinced that the filtrate experiments prove the 
theory of infection, for all the cells were surely removed. He feels 
that the fact that the- virus passed through a rather thick-walled Berke- 
feld filter demonstrates that it is an invisible filtrate virus. He clearly 
shows that the leukaemic virus can be separated from the virus 
of tuberculosis by filtration and that, therefore, the two diseases 
are distinct. Starting with an emulsion of spleen taken from an 
animal, both leukaemic and tuberculous, in which tubercle bacilli had 
been demonstrated, he passed this through a porcelain (Eeichel) filter 
and with the filtrate he produced leukaemia with complete absence of 
tuberculosis in all the inoculated animals. 

Ellermann finally states that both the spontaneous and the trans- 
mitted leukaemia occur in two types; (a) myeloid, (b) lymphatic. In 
the first the blood is characterized by the presence of numerous 
myelocytes and transitional cells, occurring in association with a pro- 
nounced myelosis (large deposits of myelocytes) in the organs. In the 



Leukcemia of the Fowl. 9 

second, the blood is characterized by a predominance of small and 
large lymphocytes (90 per cent of the total number) occurring in 
association with a pronounced lymphomatosis (numerous infiltrations 
with lymphoid cells) of the organs. Of interest is the fact that a 
myeloid type may occur in one generation and a Lymphatic in the 
next, or that both types may occur in the same generation. The 
occurrence of both types in the same stock suggests very strongly 
that both forms of leukaemia in man are due to one and the same 
infection. 

II. Studies on the Normal Fowl. 

With the hope of making the findings in the leuksemic animals more 
clear, the following brief data of the normal fowl are presented. These 
are limited to those portions of the body which are involved in 
leukaemia. They are compiled from a large number of chickens. 

EXTERNAL APPEARANCE. 

Healthy, young, adult Plymouth Eock hen. Comb, featherless 
area about eyes, and wattles bright red. Conjunctivae and buccal 
mucous membrane pink. Skin of body white with a faint yellow 
tint. Well nourished, sides of sternum covered with a thick pad of 
tissue, ribs not palpable. Average rectal temperature, 42 ° C. 

BLOOD. 

The blood for counting and smears was obtained from the vein under 
the wing, which always appears to be well filled. From a small needle 
puncture the blood flows under pressure, is thick, dark red and clots 
quickly. 

Blood-count. — The nuclei-containing red blood cells of the fowl 
make it practically impossible to count the white blood cells by the 
usual direct method. After laking the former, one cannot differ- 
entiate between the nuclei of the two types of cells. It was there- 
fore necessary to resort to the indirect method, i. e., to determine the 
proportion of white to red cells from a stained smear, count the total 
number of cells, both whites and reds, by the direct method, and then 
calculate the total number of each present. 

The red blood cells vary somewhat : lowest limit, 2,500,000 ; highest, 
4,500,000 ; average, 3,000,000-4,000,000 per c. mm. White blood cells : 



10 Harry C. Schmeisser. 

the extreme limits are between 20,000 and 80,000 per c. mm. Propor- 
tion of whites to reds, lowest limit, 1/40 ; average, 1/50-1/150. 

Hoemoglohin (Sahli). — This shows considerable variation, lowest 
limit, 45 per cent ; highest, 75 per cent; average, 60-70 per cent. 

Blood Smears. — Wilson's stain was found to give the best results, 
especially when applied immediately after the smears were made. 

Classification of blood cells (Fig. 1). 

Erythrocyte. 

1. Normocyte (a) : Elliptical disk. Nucleus, same shape as cell, 
deep blue, slightly picnotic. Cytoplasm yellow and glassy. (Both cell 
and nucleus uniform in size, shape and staining) . 

Blood Platelet (&). 

Length of normocyte, width less than that of normocyte. Nucleus 
round, purple, chromatin diffuse, diameter equal to width of its 
cell. Cytoplasm pale gray with vacuoles about nucleus, frequently con- 
taining small circumscribed red structures. May vary in size and 
shape. 

Leucocytes. 

1. Polymorphonuclear leucocyte with eosinophilic rods (c) : Round, 
diameter about length of normocyte. Nucleus has two or more lobes, 
pale blue, chromatin diffuse. Cytoplasm colorless with bright red, 
spindle-shaped rods. 

2. Polymorphonuclear leucocyte with eosinophilic granules (d) : 
About the same in shape and size. Nucleus has two or more lobes, 
purple, slightly picnotic. Cytoplasm faintly blue with dull red 
granules. 

3. Lymphocyte {e, e') : Eound, diameter about width of normocyte. 
Nucleus round, purple, chromatin diffuse. Cytoplasm small in amount, 
to one side of nucleus, pale blue. Same cell may be slightly larger. 
Thus a division into the small (e) and large (e') lymphocyte may be 
made. 

4. Large mononuclear cell (/) : Eound or oval, diameter about 
length of normocyte (at times, more or less). Nucleus round, oval or 
slightly irregular, and larger, otherwise similar to nucleus of 
lymphocyte. Cytoplasm abundant, completely surrounds nucleus, pale 
blue. (A suggestion of fine granules.) 



Leukcemia of the Fowl. H 

5. Mast cell (g) : About same size and shape. Nucleus round or 
oval, very pale blue. Cytoplasm abundant, colorless, mostly to one 
side of nucleus with purple granules, some scattered over nucleus. 

Differential Count, 300 Cells. 

Per cent. 

Polymorphonuclear with eosinophilic rods 29.6 

Polymorphonuclear with eosinophilic granules 4.3 

Lymphocyte ^^.3 

Large mononuclear cell 19-4 

Mast cell 2.2 

Unclassified cells 2,2 

100.0 
AUTOPSY PROTOCOL. 

The following findings would correspond to those in a fowl of the 
average size and weight (1760 gm.) of the animals injected. 

Subcutaneous Fat Abundant (Fig. 4). Thick muscle pad covering 
the skeleton (Fig. 4). Inner surface of skin slightly yellow. 

Cervical Lymph-glands* (Figs. S, a and h). Sometimes difficult to 
find. Present as two chains, each consisting of six to ten glands, 
one on each side of neck, lying upon the internal jugular vein, buried 
in fat, and extending from the middle of neck to base of heart. They 
are delicate, elliptical, flat, lobulated bodies, averaging 1 x .5 x .3 cm. 
The parenchymatous lobules are pink and separated from each other 
by narrow septa of fat. No other lymph-glands were found in the 
entire body. 

Thyroids and Parathyroids.— Two of each gland. The thyroid, a 
dark red, translucent, spindle-shaped body, 1 x .4 x .4 cm., with 
just visible colloid-filled acini, separated by delicate gray septa. The 
parathyroid is attached to its lower pole. This is a small bluish- 
white sphere, 2 mm. in diameter. Thus, in pairs, they are found, one 
pair on each side of the body, just above the heart. 

Peritoneal Cavity (Fig. 4).— An omentum composed entirely of fat, 
1 cm. in thickness, takes its origin from the anterior surface and lower 
margin of the gizzard, extending over coils of intestine, etc., holding 

* Kon ' considers these structures the thymus. He * and Ellermann " " 
state that the fowl has no lymph-glands. Soshestrenski ' asserts their 
existence by stating that in his case they were not enlarged. 



12 Harry C. Schmeisser. 

them against the posterior peritoneal wall. It is fastened to the 
parietal peritoneum, laterally, and at the pubis. The lower margins of 
the right and left lobes of the liver extend down between the sternum 
and omentum to within 3 em. of the tip of the xiphoid. 

Liver (Fig. 4). — The first organ which presents itself on removing 
the sternum. Eight lobe measures 7.5 x 4.5 x 2 cm. ; left lobe, 6.5x5x2 
cm. Total weight 50 gm. or 2.8 per cent of body weight. Uni- 
formly reddish brown with smooth and glistening surface, soft and 
friable. Lobule about pin-head in size, center darker than periphery ; 
usually distinct, at times difficult to see. The cut surface shows small 
blood-vessels on cross and longitudinal section. The lobulation is less 
readily seen. 

Spleen (Fig. 6). — Lies just behind the liver. Measures 2 x 1.5 x 1 
cm., weighs 1 gm., or .05 per cent of body weight. It is small, soft, 
reddish brown. Beneath its smooth and glistening capsule, may be 
seen bluish white Malpighian bodies, slightly larger than pin-points, at 
times indistinct. On section, the capsule appears very delicate; 
trabecule are few, but usually definite, containing gaping blood-vessels. 
Malpighian bodies at times are prominent. Pulp does not rise above 
edge of capsule. 

Heart. — Lies within a delicate, transparent pericardium, containing 
a small amount of clear serum. Myocardium is uniformly reddish 
brown. 

Lungs. — Bright red and of a characteristic construction, consisting 
of a mass of entwined air tubules with large lumina and spongy walls, 
separated from each other by a small amount of vascular connective 
tissue. On section, this construction becomes more pronounced. The 
wall of each air tubule projects as a pale ridge, separated from its 
neighbor by a red linear depression, in which blood-vessels are common. 

Gastro-intestinal Tract, Pancreas and Adrenals. — These are of little 
interest except that beneath the serosa of the lower half of the intestine 
are frequently seen pearly nodules, less than a pin-head in size. 

Mesentery. — A delicate, cobweb-like membrane with some fat, but 
no demonstrable lymph-glands. 

Kidneys. — Measure 6.5 x 1.7 x 1 cm., and weigh together 12 gm., or 
7 per cent of body weight. They are uniformly reddish brown with a 
slightly nodular surface. 

Bone-marrow. — Taken from long bones of upper and middle third 
of leg. It is very soft, semifluid, bright red, mottled with yellow, i. e.. 



Leukcemia of the Fowl. 13 

rich in red blood cells and fat. Lower part of middle third frequently 
consists of a solid, yellow column of fat. The marrow cavity may be 
almost occluded by bony septa. 

MICKOSCOPICAL EXAMINATION. 

Cervical Lymph-gland. — Section shows lobules of parenchyma, 
separated by fatty tissue. Each lobule is surrounded by a delicate 
fibrous capsule and contains a very fine reticulum, in which the 
lymphocyte is diffusely scattered. This is a small, round cell with a 
round, deeply staining, picnotic nucleus, usually incompletely sur- 
rounded by a narrow rim of pink cytoplasm. Sometimes red blood 
cells are associated with the lymphocyte, but mostly they are confined 
to and form the sole occupants of the numerous capillaries. They 
appear as elongated, yellowish-pink cells, with a solid black rod or dot 
for nucleus, according to whether this is seen in longitudinal or cross 
section: Scattered through the lobule are small, sharply outlined, 
hyaline structures, which Kon ' considered as corresponding to Hassall's 
corpuscles of the thymus. 

Thyroid. — Consists of polyhedral acini, which vary in size, are lined 
with cubical epithelium and filled with granular colloid. They are 
separated from each other by a small amount of fibrous tissue, rich 
in blood capillaries. Sometimes accumulations of lymphocytes may be 
seen near the larger vessels. 

Parathyroid.— ^\i\\m its capsule is seen a prominent reticulum filled 
with closely packed cells, whose nucleus is round or oval, semivascular 
and larger than that of the lymphocyte. 

Liver. — The lobule is difficult' to limit. Periportal spaces are not 
easy to find. They consist of one or several arteries, a vein, one or 
several gall-ducts, and very little or practically no fibrous tissue, usually 
free from infiltrated cells, although lymphocytes may be present dif- 
fusely or in small follicles. The liver cells are arranged in trabeculge, 
separated by capillaries. All blood-vessels and capillaries are filled 
exclusively with red blood cells. 

Spleen. — The Malpighian bodies are indistinct, numerous, closely 
packed, composed of masses of lymphocytes surrounding very small 
arteries. Eed blood cells are limited to the pulp, where they occur 
more or less in clusters, although one is unable to demonstrate sinuses 
or inclosures of any kind. The lymphocytes are also diffusely scattered 
throughout the pulp. Veins tend to be rich in lymphocytes and 
poor in red blood cells ; the artery shows the opposite picture. 



14 



Harry C. Schmeisser. 



Lung. — Presents a characteristic structure, entirely different from 
that in the human lung. The tubules mentioned in the macroscopical 
description are seen in cross, oblique, or longitudinal section, forming 
large polyhedral units with wide walls composed of capillaries. The 
intercapillary air spaces communicate with each other and with a large 
central lumen. The latter is lined with a narrow band of smooth 
muscles surmounted by endothelium, frequently cuboidal. The inter- 
tubular fibrous tissue is small in amount, and contains large blood- 
vessels, whose branches extend into the capillary bed. These structures 
are closely packed with red blood cells. Only occasionally does one see a 
lymphocyte. The bronchi resemble those of the human lung. Follicles 
of lymphoid cells are frequently found in the submucosa or outside of 
the bronchi near arteries. 

Bone-marrow. — A low-power picture is very similar to human resting 
marrow, i. e., one sees a framework of fatty tissue inclosing nests of 
marrow cells. Arteries are filled solely with red blood cells. Venous 
spaces are difficult to determine.. 

Classification of Marrow Cells. — Very thin paraffin sections were 
stained with hsematoxylin and eosin and studied under the oil- 
immersion lens. The same cells appear slightly different under these 
conditions than when seen in the Wilson smears of normal and leukaemic 
blood. 

Erythrocytes. 

1. Normocyte (a) : Elongated, varying in shape, due to pressure. 
Nucleus a solid, black rod or dot (longitudinal or cross section). 
Cytoplasm yellowish-pink and glassy. 

2. Normoblast (&) : Round, diameter about width of normocyte. 
Nucleus round, uniformly black. Cytoplasm pink or faintly blue, and 
glassy. Frequently a narrow clear zone is seen about the nucleus. 

3. Megaloblast (&) : Same, larger, about length of a normocyte. 
Nucleus slightly picnotic. 

Leucocytes. 

1. Polymorphonuclear myelocyte with eosinophilic rods * (c) : 
Eound, Nucleus, two or more solid black lobes. Cytoplasm colorless 
with bright red, spindle-shaped rods. 



* These are obviously the polymorphonuclear with eosinophilic rods, the 
polymorphonuclear with eosinophilic granules and the large mononuclear 
cell of the normal blood. 



Leukcemia of the Fowl. 15 

2. Polymorphonuclear myelocyte with eosinophilic granules * (&) : 
Eound, about same size. Nucleus has two or more slightly vesicular 
lobes. Cytoplasm colorless with bright red granules. 

3. Mononuclear myelocyte with eosinophilic granules {a) : Eound, 
or oval, varying in size, mostly larger than 1 and 3. Nucleus round, 
oval, or horseshoe-shaped, eccentric, slightly or very vesicular. Cyto- 
plasm colorless with bright red granules. 

4. Large mononuclear myelocyte * {d) : Kound, slightly larger. 
Nucleus round, very vesicular, one or more nucleoli. Cytoplasm baso- 
philic, moderate in amount. 

Reticular Cell. — Branched. Nucleus elongated, vesicular, several 
nucleoli. Cytoplasm pink, giving off delicate fibers to form reticulum. 

Lymphocytes, mast cells, platelets, mitoses of red and white cells 
were not seen. Letters in ( ) border of predominance. 

Heart, Pancreas and Kidney : For all practical purposes similar to 
the human. 

III. A Case op Spontaneous Leukaemia. 

On October 31, 1912, a typical case of leukaemia of the fowl was 
brought to the pathological laboratory. The animal, a Plymouth Eock 
hen, had just been killed, and its body was still warm. Nothing is 
known of its clinical history. An abstract of the findings is here 
given. 

BLOOD. 

The study of the blood was limited to smears taken from the heart 
just after the animal had been received at the laboratory. They were 
stained by Wilson's method. A detailed description of the cells of 
leuksemic blood will be reserved for the experimental leuksemia where 
far better opportunities for careful study of the same were offered. 
Suffice it here simply to enumerate and briefly comment upon those 
cells which were present. 

Blood Smears. There was an enormous increase in the white blood 
cells, the proportion of whites to reds being 1 : 1.3. The predomina- 
ting cells were the large mononuclear and the mononuclear myelocyte 
with eosinophilic granules. The latter is abnormal to the blood, 

* These are obviously the polymorphonuclear with eosinophilic rods, the 
polymorphonuclear with eosinophilic granules and the large mononuclear 
cell of the normal blood. 
2 



16 Harry C. Schmeisser. 

normal to the bone-marrow, and when extramedullar is typical of 
leukaemia. Lymphocytes and polymorphs were strikingly decreased. 
Of the latter those with red granules and the mast cell were rare. 
Mitoses of the large mononuclear were common. The red blood cells 
appeared to be poor in haemoglobin and showed anisocytosis, 
poikilocytosis and polychromatophilia. These cytoplasmatic changes 
were usually associated with an increase in the size of the nucleus. 
Premature red blood cells, normoblasts and megaloblasts were present in 
large numbers. 

Differential Count, 300 Cells. 

Per cent. 

Polymorphonuclear with eosinophilic rods 8 

Pol5rmorphonuclear with eosinophilic granules 

Lymphocyte 2 

Large mononuclear cell 30 

Mast cell 

Monuclear myelocyte with eosinophilic granules 52 

Unclassified cells 8 

100 
AUTOPSY PROTOCOL. 

The animal was of medium size ; the weight was not taken. 

External Appearance. — Comb, featherless area about eyes, and 
wattles of an ash color. Buccal mucous membrane and conjunctivas, 
very pale. Anterior chamber of left eye filled with an old blood- 
clot. Eight eye normal. A moderately firm slightly nodular tumor, 
3.7 X 2 X 1.5 cm., occupied the triangular space on the left side of 
head between the angle of the mouth, ear and angle of the lower jaw, 
extending below the ramus of the latter. Subcutaneous fat was 
practically absent. Emaciation was extreme and there was marked 
muscular atrophy. A second, slightly smaller tumor, 1.7 x 1 x 1 cm., 
was found just inside the ramus and below the orbit, apparently 
commimicating over the ramus with the first growth and continuous 
below with a slightly larger, third mass.* 

Cervical Lymph-glands. — Somewhat enlarged. Lobulation indis- 
tinct. 

* A more detailed description and study of these tumors will be reserved 
for a future communication. 



Leukcemia of the Fowl. 17 

Peritoneal Cavity. — Omental fat entirely absent. Lower margins of 
right and left lobes of liver extended almost to the pubes, i. e., far 
below xiphoid. 

Liver. — Enormous. Dimensions and weight not taken. Its surface 
Avas extremely mottled. It was reddish brown and specked with 
innumerable gray or slightly yellow spots from a pin-point to a few 
millimeters in diameter, frequently closely packed to form irregular 
areas, the largest 1 cm. in diameter. In addition there were scat- 
tered gray or slightly yellow nodules, averaging about 2, mm. in 
diameter. Sectioned surface similar in appearance. The blood-vessels 
were surrounded by a gray zone. 

Spleen. — Enormous. Dimensions and weight not taken. It was 
about the size of a small hen's egg. Diffusely gray. 

Heart. — At the apex there were several gray spots, pin-point in size. 

Kidneys. — Greatly enlarged. Both showed nodules, similar to those 
in liver. 

Bone-marrow. — Abundant, gray, with absence of fat. 

Thyroids, Parathyroids, Lungs, Gastro-intestinal Tract, Pancreas 
and Adrenals. — Apparently uninvolved. 

MICROSCOPICAL . EXAMINATION. 

Cervical Lymph-glands. — The normal structure was somewhat 
changed. There was complete disappearance of the interlobular fat 
with approximation of the greatly swollen parenchymatous lobules. 
Here and there Avere intra- and inter-lobular foci of myeloid tissue. 
These frequently enclosed an artery or vein. There was also a more 
diffuse infiltration of the parenchyma by myeloid cells, filling capillaries, 
veins, arteries and in places breaking through the lobular capsule into 
the interlobular tissue. Of the infiltrating cells two predominated : (1) 
A large mononuclear, usually round, at times slightly polygonal due to 
pressure, with a single, round, oval, or indented, vesicular, at times 
multiple, nucleus with one or more nucleoli. Its cytoplasm was non- 
granular and slightly basophilic. (2) The mononuclear myelocyte 
with eosinophilic granules, described under normal bone-marrow. 
Mitoses of these two cells were quite common. Normoblasts and 
megaloblasts appeared to be present. 

Liver. — Here the process was most extreme. Very little liver tissue 
remained. Everywhere were closely packed masses of myeloid cells 
from which the liver trabeculae had completely disappeared. These 



18 Harry C. Schmeisser. 

masses of cells surrounded blood-vessels, both arteries and veins, infil- 
trating the walls of the latter and filling the lumina of both. Within 
the vessels the white blood cells were present in about equal proportion 
with the red blood cells. Between these more focal accumulations the 
myeloid cells had infiltrated in a more diffuse manner between the liver 
columns, spreading them apart. It was usually difficult to demonstrate 
the capillary wall. Hepatic cells in these locations did not suffer so 
much. Some of the above-mentioned, circujmscribed infiltrations 
showed a coarse sclerosis. The same infiltrating cells were present as 
in the cervical lymph-glands, with a prevalence of the large mononu- 
clear, which was very rich in mitoses, and the mononuclear myelocyte 
with eosinophilic granules. The two types of polymorphonuclear cells 
and the premature red blood cells were present in fewer numbers. 

Spleen. — Pulp diffusely infiltrated with closely packed leuksemie 
cells, which crowded the reticulum, distended the blood-vessels and 
separated and compressed the Malpighian bodies. The mononuclear 
myelocyte with eosinophilic granules, although present, was scarce. 
The large mononuclear, frequently showing mitoses, was the common 
cell. 

Heart. — The intramuscular capillaries, were moderately distended 
with the large mononuclears and red blood cells, present in about equal 
proportion. The former had also infiltrated between the muscle fibers. 
The mononuclear myelocyte with eosinophilic granules was only occa- 
sionally seen, both within and without the blood-vessels. 

Lungs. — The intertubular blood-vessels, their branches which extend 
into the capillary bed, and also the capillaries, were distended with 
leukaemic blood, in which the large mononuclear seemed to exceed the 
red blood cell. Mitoses were common. Infiltration of the tissue was 
limited to two foci of myeloid cells. The one was composed principally 
of the mononuclear myelocyte with eosinophilic granules and the large 
mononuclear. Mitoses, especially of the first cell, were seen. Both 
types of polymorphs were also present. The other focus was composed 
exclusively of premature red blood cells, normoblasts and megaloblasts 
showing mitoses. 

Kidneys. — All the blood-vessels, from the largest to the capillaries of 
the glomerular tuft, were distended with the characteristic leukasmic 
blood. Throughout the section there was a diffuse infiltration of 
myeloid cells, especially between the convoluted tubules. Here and 
there were foci, in some of which the mononuclear myelocyte with 



LeukoBmia of the Fowl. 19 

eosinophilic granules predominated, frequently showing mitoses ; others 
seemed to be composed exclusively of the large mononuclear. Here 
mitoses were also common. In these foci the convoluted tubules had 
either been pushed aside or had atrophied. 

Bone-marrow. — This was greatly changed. It consisted of a closely 
packed mass of white marrow cells, with complete atrophy of the fat 
and great rarity of normocytes. One or two small focal areas of 
sclerosis were present. The arteries were mostly empty. Some showed 
a little blood containing a few large mononuclears. Those marrow cells, 
which were present, both red and white, answered to their descriptions 
given under normal bone-marrow, with the exception of the large 
mononuclear myelocyte, which showed considerable variation in its 
nucleus. This was either single or multiple, round, oval, or horseshoe- 
shaped. The order of predominance had changed greatly. The large 
mononuclear myelocyte was present in far greater numbers than any 
other cell, and showed extensive mitoses. The normoblast and megalo- 
blast with mitoses followed next in frequency; then the normocyte. 
Polymorphonuclear myelocytes, those with eosinophilic rods and those 
with eosinophilic granules, had disappeared entirely. Curious is the 
fact that the mononuclear myelocyte with eosinophilic granules could 
not be demonstrated with certainty. As in the normal marrow lymph- 
ocytes, mast cells and platelets were not seen. 

Thyroids, Parathyroids, Pancreas and Adrenals. — These were not 
studied. 

SUMMAEY. 

In summarizing the changes in the blood and organs, there was 
found : 

1. In the Blood. — (a) A great increase in the total number of white 
blood cells. Although a total count was not made, this increase was 
evident from the appearance of the blood smears, and of the blood- 
vessels in sections. The actual proportion of white to red cells sub- 
stantiated this fact. The differential count showed a marked increase 
of the large mononuclear cell at the expense of the other white blood 
cells of the normal blood. In addition, a true myelocyte appeared in the 
circulation. Mitoses of the large mononuclear were common, (b) A 
corresponding decrease in the total number of red blood cells. These 
showed a drop in haemoglobin, variation in size and shape, basophilic 
staining of the cytoplasm, and swelling of their nuclei. Premature 
red cells, normoblasts and megaloblasts made their appearance. 



20 Harry C. Schmeisser. 

2. In the Organs. — (a) A difEuse and circumscribed, at times 
nodular, infiltration of myeloid cells, in which the large mononuclear, 
and mononuclear myelocyte with eosinophilic granules predominated, 
although the other cells of the normal bone-marrow were at times 
present. This myelosis involved especially the liver, spleen, kidneys and 
bone-marrow, resulting in an extreme enlargement of the first three 
organs. Almost all of the remaining organs showed infiltrations, but to 
a less degree, (b) A change in the contents of the blood-vessels. The 
proportion of white to red cells was greatly increased. The predomina- 
ting cells were the same as those of the infiltration. 

CONCLUSION. 

In conclusion, if we consider that the cells, characteristic of both 
leukeemic infiltrate and blood, were the same, and that under normal 
conditions the mononuclear myelocyte with eosinophilic granules 
occurs only in the bone-marrow and the large mononuclear only in the 
marrow and blood, it is evident from the summarized facts, that the 
above case inust be considered a typical case of mtjeloid leukcemia. 

IV. Experimental Leukemia. 

With material from the above case, the disease was successfully trans- 
mitted into the fifth generation. A total of 105 animals were used in 
conducting many different kinds of experiments. Of this number, 22 
in all have developed leukaemia. In four additional animals, a definite 
diagnosis could not be established, although the appearances were highly 
suggestive. The strain has now been running for more than 13 months. 

This paper will be confined to a report of those series which deal with 
simple transmission of the disease by the injection of an organic 
emulsion. 

Five of these series were conducted, each consisting of 5, 10 or 15 
fowls. The percentage of positives per series varied from 20-40 per 
cent. Of the total number of 40 chickens injected, 13 became leukaemic, 
i. e. 32.5 per cent. In addition, a definite diagnosis could not be made 
in three, although the findings were very suggestive. 

PREPARATION OF MATERIAL, METHODS OF INJECTION, ETC. 

The material used for transmission was an emulsion of liver, and 
sometimes of spleen also. It was prepared by thoroughly macerating 



Leukcemia of the Fowl. 21 

pieces of the organ in a mortar, after the addition of .9 per cent normal 
salt solution. This was filtered through a single layer of fine linen or 
a small amount of raw cotton, thus removing the fibrous tissue suf- 
ficiently for intraperitoneal injection, although, when it was used in- 
travenously, instant death frequently resulted. Hence it was found best 
to filter also through two layers of filter paper with the aid of a suction 
pump. This filtrate was found to be absolutely fiber-free, but still con- 
tained blood and parenchymatous cells. A 15 per cent emulsion gave 
the best results. The entire preceding process, as well as the following 
steps, were carried out aseptically. 

The fowls were injected either intravenously or intraperitoneally 
with 10 cc. Both methods were sometimes combined, when a total of 
20 cc. was administered. The vein selected for injection was the large 
one under the wing. 

Animals used for transmission were young, adult hens of the same 
breed as the spontaneous case, and exemplified by the normal control. 

CLINICAL HISTORY. 

Incubation Period. — This is usually from five to six weeks. In rare 
cases, it may reach a maximum of 16 weeks. 

Signs and Symptoms. — The onset is usually rather abrupt, preceded 
by no definite premonitory symptoms. The animal, which has pre- 
viously appeared entirely normal, begins to show a slight but progres- 
sive, at times a sudden and intense, pallor of its comb, the featherless 
area about the eyes and the wattles. This is almost invariably associated 
with jaundice, which is likewise progressive and usually reaches an 
extreme grade. The combination of intense pallor and jaundice results 
in a characteristic, yellowish-pink color, which gives the fowl a ghastly 
appearance. The comb may be surprisingly red or extremely pale with- 
out jaundice. The animal emaciates rapidly and to an extreme degree. 
The actual loss in weight during the disease is striking and best illus- 
trated by the following figures. No. 28, on the day of the onset of the 
disease, weighed 1484.5 gm. The duration of the disease was three 
weeks, four days. At death the weight was 897 gm. Therefore, there 
was a loss of 587.5 gm. in 25 days, or at rate of 23.5 gm. per day. 

At first the bird acts entirely normally, or it may appear slightly ill. 
In a few days, however, it acts as if it were very sick, stops eating and 
drinking, and stands about with head retracted, eyes closed and tail 
drooping. It prefers to assume a squatting position. If made to move 



22 Harry C. Schmeisser. 

it does so very slowly and carefully. Weakness becomes more and more 
marked, until on the last day it lies prostrated, with its head on the floor, 
wings drooping, eyes closed and at times is dyspnoeic. 

Fever has never been observed. 

Duration of the Disease. — This is most frequently from one to two 
weeks. One case exceptionally acute lasted only 33 hours. Two cases, 
three days. The longest course was four weeks, four days. 

'Prognosis. — Having once begun, the disease progresses steadily to a 
fatal issue. Only in one case out of 23 leuksemic animals did a spon- 
taneous cure result. 

BLOOD. 

In Gross. — With the onset of anamia, the vein under the wing col- 
lapses and the blood undergoes a change. It soon flows with the great- 
est ease and rapidity, resembles pale yellow water and shows no tendency 
to clot. The animal apparently would bleed to death from a pin-point 
wound, if the haemorrhage were not artificially arrested. 

Blood-count. — In most cases there is a progressive and extreme de- 
crease in the total number of red blood cells. At onset the count may 
be but slightly below normal, 2,224,000, while just before death it, at 
times, reaches 630,000. More commonly, the lowest point ranges 
between 1,112,000 and 1,408,000 per c. mm. In one case, the count 
remained normal. 

The count of white cells is invariably high, between 131,200 and 
210,000 per c. mm. 

Eatio of W/E = 1/3-1/9. 

Ecemoglobin. — This usually falls steadily and reaches a very low 
point. From slightly below normal, 40-50 per cent at onset, it fre- 
quently drops to 10-15 per cent just before death. In several cases it 
fell only to 23 per cent. In one case there was no change at all. 

Blood Smears. — The morphology of the leuksemic blood is excep- 
tionally interesting. In addition to the enormous increase in the num- 
ber of white cells, all of the cellular elements show marked changes and 
many new forms make their appearance. Smears were stained by Wil- 
son's method. 

Classification of blood cells (Fig. 2). 

Erythrocytes. 

1. Normocyte: (a) Normal (a), except for variation in the 
amount of hemoglobin, (b) Showing anisocytosis, poikilocytosis and 



Leukcemia of the Fowl. 23 

polychromatophilia, mostly associated with a swelling of the nucleus 
and separation of its chromatin (6). 

2. Normoblast (c) : Eound, diameter less than length of normal 
normocyte. Nucleus round, of same color or slightly purple, but larger 
and with more scattered chromatin than nucleus of normal normocyte. 
Cytoplasm greenish-blue and glassy. Frequently with clear zone about 
nucleus. 

3. Megaloblast {d) : Same, except diameter equal to or greater than 
length of normal normocyte. 

4. Mitotic Cells (e) : All stages, from monaster to complete division 
of nucleus, (a) Eound or elliptical, diameter about length of normal 
normocyte. Dense, deep blue chromosomes, massed in center of cell. 
C3rtoplasm greenish-blue and glassy, (b) Same, with two masses of 
chromosomes in opposite extremes of cell, (c) Same (at times with a 
slight constriction in the middle of the cell) with irregular, dense, deep 
blue or slightly purple chromatin masses in place of individual chromo- 
somes, (d) Same, with two nuclei, similar in appearance to those of 
normoblast, (e) Same as normal normocyte with two nuclei, similar in 
appearance to those of normoblast, but only slightly larger than nucleus 
of normal normocyte, (a), (b), (c) and (d) may show polychroma- 
tophilic cytoplasm. 

Blood Platelets (/). 

1. Same as normal, except that cell and nucleus are both larger. 

2. Larger than normal with two nuclei. 

Leucocytes. 

1. Polymorphonuclear leucocyte with eosinophilic rods {g) '. Same 
as in normal blood, at times possibly a little smaller. 

2. Polymorphonuclear leucocyte with eosinophilic granules (/i) : 
Same as in normal blood, at times possibly a little smaller. 

3. Lymphocyte (t) : Same as in normal blood. 

4. Large mononuclear cell : (a) As described in normal blood, with 
a little less cytoplasm, (b) Same size to one half times larger than (a), 
with both nucleus and cytoplasm paler (;). (a) and (b) cannot be 
separated absolutely. Every gradation, (c) Mitoses (fc) : All stages, 
from monaster to complete separation of nucleus, (a') Elliptical, 
diameter about one and a half length of normal normocyte. Dense, 
purple chromosomes centrally massed. Cytoplasm pale bluish-gray, 



2-i Harry C. Schmeisser. 

granular, (b') Same, with two masses of chromosomes in opposite ex- 
tremes of the cell, (c') Same, with two purple nuclei, (d') Same, with 
three purple nuclei. 

5. Mast Cell {I) : As described in normal blood. 

6. Mononuclear myelocyte with eosinophilic granules {m) : Eound 
or slightly elliptical, diameter about length of normal normocyte or 
longer. Nucleus, oval, pale blue with dense chromatin, eccentric. 
Cytoplasm colorless with small and large, bright red granules, some 
scattered over granules. 

Cytoplasmatic Masses without Nuclei {n) : Eound or slightly oval; 
diameter varies, usually about width of normal normocyte. No nucleus. 
Cytoplasm grayish-blue, sometimes with vacuoles. 

This, then, is the blood picture common to all the leuksemic cases. 
The order of predominance of the white cells is typical of leukgemia, 
differing from the normal, but agreeing with that of the spontaneous 
case. The large mononuclear is present, by far, in greatest numbers. 
The other cells of the normal blood are decreased. The polymorphonu- 
clear with eosinophilic granules and the mast cell are very scarce. The 
mononuclear myelocyte with eosinophilic granules, although not as 
common as in the spontaneous case, can usually be demonstrated in 
every leuksemic animal. 

The platelets are greatly increased in number. 

Differential Count, 300 Cells. 

Per cent. 

Polymorphonuclear with eosinophilic rods 6 

Polymorphonuclear with eosinophilic granules 

Lymphocyte 4 

Large mononuclear cell 86 

Mast cell 1 

Mononuclear myelocyte with eosinophilic granules ... 1 

Unclassified cells 2 

100 
AUTOPSY FINDINGS. 

The weight of the animal in every case was far below its weight before 
injection.* Two lowest weights, at autopsy, were 675 and 897 gm. 

External Appearance. — The jaundice was found at times to involve 
the skin of the entire body.f The conjunctivge and buccal mucous mem- 

* Animals which remained negative invariably gained in weight. 
t Probably this was more frequent but not recognized, except when very 
grave, because of the normal yellow tint of the skin. 



Leukcemia of the Fowl. 25 

branes were always very pale. The eyes, nose and mouth were never 
involved. There was extreme emaciation, and great scarcity or entire 
absence of subcutaneous fat. Muscular atrophy was usually marked, at 
times practically only the skeleton remained ( Fig. 5 ) . 

Cervical Lymph-glands. — Macroscopically, these were usually unin- 
volved. In two cases they were definitely enlarged (Pig. 3, a and b) , in 
the one very much so, measuring 1.5 x 8 x 4 cm. and 2 x 1 x .5 cm., 
respectively. They appeared uniformly gray. The lobules of the par- 
enchyma were enlarged and the interlobular fat had disappeared. In a 
third case, they were of normal size and appearance, but showed several 
gray nodules, 1 mm. in diameter. Microscopically, those glands w^hich 
appeared normal in gross were usually free from myeloid infiltration, 
although their blood-vessels contained leukemic blood. The diffusely 
enlarged glands showed a marked swelling of their parenchyma, with 
complete atrophy of the interlobular fat. Myeloid cells, both the large 
mononuclear and the mononuclear myelocyte with eosinophilic granules, 
were scattered through the lobules. Foci, some composed entirely of 
the first, and others exclusively of the second, were localized principally 
in the interlobular connective tissue. They were rich in mitotic figures. 
The gray nodules seen in gross proved to be masses of proliferating 
myeloid cells. All the blood-vessels were filled with the characteristic 
blood. 

Thyroids and Parathyroids. — These were grossly and microscopically 
uninvolved, with the exception of the blood-vessels, which were filled 
with leuksemic blood. 

Peritoneal Cavity. — In every case the omental fat was greatly de- 
creased. At best, it was present only in moderate amount. As a rule 
it was replaced by a thin yellow membrane. Ascites occurred in six out 
of 13 cases, at times in sufficient quantity to distend the abdomen. It 
was always associated with a sero-fibrinous mass, which covered not only 
the liver and most of the other abdominal viscera, but also spread over 
the outer surface of the pericardium. 

With enlargement of the liver, the lower margins of its two lobes 
change their position in relation to the tip of the xiphoid. They 
descend to this landmark and frequently extend far beyond. With the 
exception of N'os. 31 and 70, every animal of the 13 had an enlarged liver 
(Table 1) . The margins of the right and left lobes of the smallest of the 
enlarged livers were, respectively, 1 and 3 cm. above the xiphoid, while 
the margins of the largest liver extended 3.5 and 3 cm., respectively, 



26 Harry C. Schmeisser. 

below it. In fact, the latter organ in situ (Fig. 5) was so enormous that 
it filled the entire peritoneal cavity and was the only viscus visible on 
entering the abdomen. 

Liver. — As mentioned, the liver was greatly enlarged in 11 cases 
(Table 1), frequently enormous (Fig. 5). In the smallest of these 
the right lobe measured 9 x 4.5 x 3,8 cm. ; the left lobe, 7 x 5 x 3,8 cm. ; 
in the largest, right lobe 13.5 x 4.5 x 4 cm. ; left lobe 12.5 x 4 x 3.5 cm. 
On comparing them with the normal, these dimensions are not very con- 
vincing, with the exception of the length of the lobes. As the organ 
enlarges, it becomes distorted, because the limited cross-diameter of the 
peritoneal cavity prevents its expansion in this direction and forces the 
lobes to follow the costal framework, posteriorly. The long diameters 
of the lobes are more reliable, because the organ can enlarge freely in 
this direction. 

The weight of the liver is a more accurate indication of its size, 
especially when expressed in per cent of body weight, i. e., the number of 
grams of weight of organ per 100 gm. of weight of the animal at death. 
Thus, the weights were found to range from 80-265 gm, i. e., they were 
over five times the normal or 6.2-10.3 per cent of body-weight, an 
increase of 3.6 -f times the normal (Table 1). 

The external appearance of the liver may not difi^er much from the 
normal, but usually it is very characteristic (Fig. 5). It may appear 
diffusely gray, due to very closely packed subcapsular spots, pin-point to 
2 mm. in diameter. These are usually more scattered and translucent, 
at times slightly yellow and opaque. They may fuse to form larger 
areas with a diameter of 0.5-1 cm., or they may be arranged in a delicate 
gray network. In addition, numerous gray or slightly yellow nodules, 
ranging from 2-0.5 cm. in diameter are often present. The whole gives 
the surface an extremely mottled appearance. Lobulation at times is 
visible, usually indistinct. The liver may be slightly firm or friable. 
The sectioned surface appears very similar to the external surface. Dots 
and lines often form gray borders along the blood-vessels. The latter 
also occupy the centers of some of the larger, circumscribed, gray areas. 
The perivascular connective tissue in rare instances is bile-stained. 
Microscopically, there is usually a diffuse infiltration of myeloid cells. 
They are closely packed within and without the intralobular capillaries. 
The liver trabeculse show fatty degeneration and atrophy. The large 
mononuclear, rich in mitotic figures, is by far the predominating cell. 



LeuTccemia of the Fowl. 27 

The mononuclear myelocyte with eosinophilic granules is very scarce. 
Scattered through the section are also foci of large mononuclears, or of 
mononuclear myelocytes with eosinophilic granules. Some contain both 
types of cells. They abound in mitotic figures. The liver cells in these 
foci have entirely disappeared. The small, gray nodules consist of cir- 
cumscribed masses of myeloid tissue, usually occupying the periportal 
spaces and composed of a central portion of large mononuclears sur- 
rounded by the mononuclear myelocyte with eosinophilic granules. In 
the blood-vessels and capillaries, the large mononuclear, at times, seems 
to greatly exceed the red blood cell in numbers. 

Spleen. — Except in ISTos. 31 and 70, the spleen in every case was en- 
larged (Table 1) ; usually very much (Fig. 6). The dimensions, in 
contrast to those of the liver, are of definite comparative value. The 
smallest of the enlarged organs measured 3 x 2 x 1.7 cm., the largest 
4 X 3 X 2.3 cm., the latter being just twice the normal in every 
dimension. 

The weights were strikingly increased. The lowest was 6 gm., the 
highest, 18 gm., i. e. 18 times the normal, or .6-1.6 per cent of the body 
weight, i. e., 32 times the normal. 

The surface of the spleen may look normal, be reddish brown and 
show beneath its capsule pin-point, gray Malpighian bodies. More fre- 
quently one sees scattered, gray or slightly yellow spots and nodules 
(Fig. 6), the first from 1-3 mm., and the largest of the second from 
0.5-1 cm. in diameter. Again, the organ appears just diffusely gray. A 
section (Fig. 6) appears usually the same as the surface. When dif-* 
fusely gray, the pulp is somewhat granular and bulges. Microscopically, 
the entire pulp may be diffusely infiltrated with the large mononuclear 
cell, separating and compressing the Malpighian bodies. In addition, 
circumscribed, closely packed masses of pure large mononuclears or 
mononuclear myelocytes with eosinophilic granules are scattered 
through the section. Again, the myelosis may be present only in 
foci, with practically no disturbance of the normal splenic structure. 
Mitoses are abundant wherever the large mononuclear occurs. The con- 
tents of the blood-vessels are the same as in the liver. 

Heart. — As mentioned above, the external surface of the pericardium 
is frequently covered with a serofibrinous mass. The heart itself may be 
somewhat enlarged, otherwise it appears normal (Fig. 5). Micro- 
scopically also there is little to be seen besides a great excess of the large 



38 Harry C. Schnieisser. 

mononuclear in the intramuscular capillaries, with an occasional small 
extravascular focus of infiltration, consisting of the same cell. 

Lungs. — These are seldom involved. In two cases they were cedemat- 
ous. In one, the tubular walls were wide and gray, occluding the 
lumina. On section, the latter case presented a similar but more marked 
picture. Microscopically the intertubular blood-vessels, their branches 
which extend into the capillary bed, and the capillaries themselves, are 
always filled with leukaemic blood. At times they are greatly distended. 
The white cells are always increased in number, and sometimes the 
blood seems to consist solely of closely packed, large mononuclears. 
Mitoses are everywhere abundant. Very rarely, a few mononuclear 
myelocytes with eosinophilic granules or large mononuclears are gath- 
ered in small masses in the intertubular connective tissue. 

Gastro-intestinal Tract, Pancreas and Adrenals. — These in gross 
showed nothing of interest. No mesenteric lymph-glands were demon- 
strated. The pancreas, microscopically in no case showed any infiltra- 
tion of its parenchyma proper, but in several there were numerous nests 
of myeloid cells in the interlobar fat tissue, usually surrounding one or 
more capillaries, and composed of the large mononuclear, eosinophilic 
myelocytes, both mononuclear and polymorphonuclear. Mitoses of both 
the mononuclears were frequent. The blood-vessels in the parenchyma 
and fatty tissue contained, as usual, the predominating large mononu- 
clear. 

The adrenals also reveal interesting findings histologically. It is 
quite common for the intertrabecular capillaries to be enormously dis- 
tended with the characteristic leuksemic blood and for the myeloid cells 
to have infiltrated between the capillary wall and parenchymatous cells. 
These nests contain mostly the large mononuclear, but now and again 
they seem to be very rich in lymphocytes. The parenchyma has suffered 
greatly; its nuclei stain poorly and frequently its cells show disinte- 
gration. 

Kidneys. — Of the 13 cases, the kidneys of five were enlarged. The 
smallest measured 7 x 1.5 x 1.3 cm., the largest 7.3 x 3.3 x 1.4 cm. The 
weight of both kidneys ranged from 13-86 gm., or 0.8-1.4 per cent of 
the body-weight. In one case the kidneys were extremely oedematous 
and weighed 33 gm. or 3 per cent of the body-weight. 

The surface and section of the kidney may appear entirely normal, 
but usually one can see, below its capsule, scattered, gray pin-point dots, 



Leukoemia of the Fowl. -29 

delicate lines, or even one or two nodules, the largest 0.5 cm. in diameter. 
Again, they may appear diffusely gray. In the one case, they were large, 
succulent and translucent, due to oedema. Microscopically, the kidneys 
always show more or less distension of their blood-vessels and inter- 
tubular capillaries with the characteristic leukgemic blood, in which 
white blood cells, at times, seem even to exceed the normocytes, and in 
which the large mononuclear predominates. When capillary distension 
is moderate, the tubules appear normal ; but at times they are so enor- 
mously over-filled as to cause extreme atrophy and degeneration of the 
tubular epithelium, resulting frequently in circumscribed areas devoid 
of any parenchyma. These areas tend to form a kind of zone about the 
larger blood-vessels. The glomeruli are surprisingly free. The walls 
and perivascular tissue of some of the vessels are infiltrated with 
actively generating myeloid cells, especially the large mononuclear. 

Bone-marrow. — This is always involved, usually more or less char- 
acteristically, being increased in amount, moderately soft and red, mot- 
tled with countless gray dots to slightly larger areas, or it may be dif- 
fusely gray. In either case the fat is absent entirely and red blood 
cells are very scarce. The marrow may be involved as a whole or only 
in part. Now and again it has been converted into a uniformly gray, 
dry and slightly firm column, which bulges from the marrow cavity. 
In such cases it is obviously very rich in white cells, poor in red cells and 
fat. Microscopically, the normal structure of the marrow is greatly 
changed. The fatty tissue has completely disappeared and the marrow 
cells are closely packed in a solid mass, in which the normocyte is 
rather inconspicuous. The arteries in the center of the marrow are 
poor in blood. One or two contain a few normocytes and large mononu- 
clears. The description of the red and white cells, which are present 
agrees with that given under normal marrow. Possibly the large 
mononuclear is more commonly polygonal, due to pressure. Mitoses of 
both the large mononuclear and the erythrocytes are common especially 
the first. The order of predominance has changed from the normal. 
The large mononuclear myelocyte is present by far in greatest numbers ; 
the normoblast, megaloblast and mononuclear myelocyte with eosino- 
philic granules follow in about equal numbers; the normocyte comes 
last. Both types of polymorphonuclear cells, as weU as the lymphocyte, 
mast cells and platelets were not seen at all. Mitoses of the mononu- 
clear myelocyte with eosinophilic granules were not demonstrated. 



30 



Harry C. Schmeisser. 



TABLE 1.— EXPERIMENTAL LEUKEMIA. 

Weights, in Grams of Body, Organs and Relation of Organs to Body 

AT Autopsy. 



Animal 
No. 


Body. 


Liver. 


Liver to 

body %. 


Spleen. 


Spleen to 
body %. 


Kidneys. 


Kidneys to 
body %. 


Normal 


1760 


50 


2.8 


1 


0.05 


12 


0.7 


1 


1515 


117 


7.7 


11 


0.7 


20 


1.3 


6 


1200 


124 


10.3 


15 


1.2 


10 


0.8 


12 


1 


95 




15 








14 


1573 


125 


i.d 


18 


'i!i 


32 » 


'2!o 


15 


1660 


116 


6.9 


10 


0.6 


20 


1.2 


24 3 










.... 






28 


"897 


"85 


'9.6 


6 


oii 






30 


1410 


107 


7.6 


17 


0.6 






31 


675 


20 


2.9 


3 


.4 


5 


6.7 


53 


• . . • 


265 




12 








57 


1070 


91 


'8.5 


18 


i'.e 


is 


i.i 


70* 




65 




4 




26 




103 


i282 


80 


6.2 


8 


0.6 


12 


0.9 



1 Not weighed. 

2 Very cedematous. 

' Whole animal kept as a museum specimen. Illustrated, Fig. 5. 
* Spontaneously cured. Not leukaemia at death. 



SUMMARY. 

In sammarizing the essential points deduced by the simple trans- 
mission of leukaemia by the injection of an organic emulsion, we shall 
consider : 

1. Clinical History. — After an incubation period, usually from five to 
six weeks, the fowl suddenly becomes pale, jaundiced, emaciates rapidly, 
loses weight and shows signs of extreme weakness, followed almost with- 
out exception by death in one to two weeks. 

2. Blood. — (a) The total number of white blood cells is greatly in- 
creased, resulting in a proportion of one white to three red blood cells. 
The differential count shows a marked increase and predominance of 
the large mononuclear over the other white cells of the normal blood, 
which have decreased. The mononuclear myelocyte with eosinophilic 
granules is present in more or less numbers in practically every case. 
Besides the normal-appearing large mononuclear, one sees many larger, 
pale forms. In these cells, mitoses, in all stages, typical and atypical, 
are common, (b) The total number of red blood cells is correspond- 
ingly decreased, with a marked fall in the haemoglobin. They present 



Leukcemia of the Fowl. 31 

variations in size, shape and staining, associated with swelling of the 
nucleus. Normoblasts, megaloblasts, with mitoses in all stages make 
their appearance, (c) There is an increase in the number of the blood 
platelets, associated with an increase both in the size of the cell and the 
nucleus. The cells frequently contain more than one nucleus, (d) The 
blood loses its power of clotting. 

3. Organic Findings. — (a) There is a diffuse, focal, less frequently 
a nodular infiltration of marrow cells, in which the large mononuclear 
and mononuclear myelocyte with eosinophilic granules predominate. 
The foci may be limited to the large mononuclear or granular eosino- 
philic myelocytes, commonly the mononuclear, or may be composed of 
both types. Extensive mitoses testify to active proliferation. This 
myelosis affects most particularly the liver, spleen, kidneys and bone- 
marrow, causing a great increase in the size of the first three organs. 
Earely, the cervical lymph-glands are also very much enlarged. Most 
of the remaining organs and neighboring tissues may contain infiltra- 
tions but not so extensive, (b)- The relative proportion of white to red 
blood cells is greatly increased in the blood-vessels. The same cells pre- 
dominate as in the infiltrations, (c) There are atrophic and degenera- 
tive changes of the parenchyma, general atrophy of the adipose tissue, 
ascites etc. 

CONCLUSION. 

The injection of an organic emulsion causes a picture of myeloid 
leukaemia in every respect similar to that of spontaneous leukaemia as it 
occurs in the fowl. 

The chemical picture and changes produced in the blood and organs 
are analogous to those which occur in human leukaemia. 

V. Conclusion. 

1. The spontaneous occurrence of myeloid leukaemia of the fowl is 
confirmed. 

2. Myeloid leukaemia in the fowl is transmissible by the intravenous 
or intraperitoneal injection of an organic emulsion. The latter is in 
confirmation of the work by Ellermann and Bang who, as I have stated, 
were the first to successfully transmit the disease. They were followed 
by Hirschfeld and Jacoby, whose successful transmissions, however, 
seem to be limited to a strain, which had its origin in a fowl presented 
to them by Ellermann and Bang. Burckhardt likewise transmitted the 

3 



33 Harry C. Schmeisser. 

disease, but here again the stock animal came from Hirschfeld and 
Jacoby, and therefore indirectly from Ellermann and Bang. 

The above reported transmission is of special interest, because it 
originated from an animal entirely independent and far remote from 
those of the previous investigators. 

Literature of Leukemia in the Fowl. 

1. Moore, V. A.: Infectious Leukaemia in Fowls — A Bacterial Dis- 

ease Frequently Mistaken for Fowl Cholera. Twelfth and 
Thirteenth Annual Reports, Bureau of Animal Industry, 
U. S., 1895-1896, 185-205. 

2. Butterfield^ E. E. : Aleuksemic Lymphadenoid Tumors of the 

Hen. Folia h^mat., 1905, II, G49-657. 

3. Warthin^ a. S.: Leukaemia of the Common Fowl. Jour. Infect. 

Lis., 1907, IV, 369-381. 

4. KoN, J. : TJeber Leukamie beim Hulm. Virchows Arch, f . path. 

Anat., 1907, CXC, 338-349. 

5. Soshestrensei, N. A.: (Leukaemia of the Chicken.) Uchen. 

zapiski Kazan. Vet. Inst., 1908, XXV, 315-222. 

6. Ellermann^ V., and Bang, 0.: Experimentelle Leukamie bei 

Hiihnern. Vorlaufige Mitteilung. Centralbl. f. Bakteriol., 
1908, Theil 1, Orig., XLVI, 4-5. 

7. Experimentelle Leukamie bei Hiihnern. Centralbl. f. 

Bakteriol., 1908, Theil 1, Orig., XLVI, 595-609. 

8. Experimentelle Leukamie bei Hiihnern. Verhandl. d. d. 

path. Gesellsch., 1908, XII, 224-225. 

(Experimental Leukaemia in Fowls.) Overs, v. d. k. 



Danske Vidensk. Selsk. Torh., Kbenk., 1908, 65-94; ibid., 
1909, p. 261. 

10. Experimentelle Leukamie bei Hiihnern. Ztschr. f. Hyg. 

u. Infektionskrankh., 1909, LXIII, 231-272. 

11. Schridde: Gribt es eine infektiose Aetiologie der Leukamie? 

Deutsche med. Wchnschr., 1909, XXXV, 280. 

12. Hirschfeld, H., and Jacoby, M. : Zur Kenntnis der iibertrag- 

baren Hiihnerleukamie. Berl. klin. Wchnschr., 1909, XLVI, 
159-160. 

13. Uebertragbare Hiihnerleukamie. Berl. klin. Wchnschr., 

1909, XLVI, 314. 



Leukaemia of the Fowl. 33 

14. HiRSCHFELD, H., and Jacoby, M.: Uebertragungsversuche mit 

Hiilmerleukamie. Ztschr. f. klin. Med., 1910, LXIX, 107- 
120. 

15. BuKCKHARDT, J. L. : (Bei del 82. Versammlung Deutscher Natur- 

forscher und Aerzte zu Konigsberg.) Ztschr. f. Immunitats- 
forsch. w. exper. Therap., 1910, Theil 2, 810-811. 

16. Ueber das Blutbild bei Hiibnertuberkulose und dessen 

Beziehungen zur sogenannten Hiihnerleiikamie, nebst Bemer- 
kungen iiber das normale Hiilinerblut. Ztschr. f . Immunitats- 
forsch. n. exper. Therap. 1912, XIV, 544-604. 

17. HiRSCHFELD^ H., and Jacoby, M. : Uebertragbare Hiihnerleukamie 

und ihre Unabhangigkeit von der Hiihnertuberciilose. Ztschr. 
f. klin. Med., 191*2, LXXV, 501-505. 

18. Ellermann, V: Unders0geler over H0nseleiikaemiens Vims. 

Urgesk. f. Laeger, 1913, LXXV, 1685-1691. 

19. TJntersuchungen iiber das Virus der Hiihnerleukamie. 

Ztschr. f. klin. Med., 1914, LXXIX, 43-48. 

Explanation of Figures. 

Fig. 1. — Normal blood of the fowl. Wilson's stain. Zeiss objective 1/12, 
eye-piece No. 3. Composite picture, (a) Normocytes, (b) Blood plate- 
lets, (c) Polymorphonuclear leucocyte with eosinophilic rods. ((?) Poly- 
morphonuclear leucocyte with eosinophilic granules, (e, e') Lymphocytes 
(small and large). (/) Large mononuclear cell, {g) Mast cell. 

Fig. 2. — Leuksemic blood of the fowl. Wilson's stain. Zeiss objective 
1/12, eye-piece No. 3. Composite picture, (o) Normal normocytes. (&) 
Normocytes showing anisocytosis, poikilocytosis, polychromatophilia, 
with swelling of nucleus and separation of its chromatin, (c) Normoblast. 
{d) Megaloblast. (e) Mitoses of erythrocytes; all stages from monaster 
to complete division of nucleus. (/) Blood platelets; both cell and nucleus 
Increased in size; increase in size with two nuclei, ig) Polymorphonu- 
clear leucocyte with eosinophilic rods, {h) Polymorphonuclear leucocyte 
with eosinophilic granules, (i) Lymphocyte, (j) Large mononuclear 
cell; same size and larger than normal with both nucleus and cytoplasm 
paler, (fc) Mitoses of large mononuclear cell; all stages, from monaster 
to complete separation of nucleus. (Z) Mast cell, {m) Mononuclear 
myelocyte with eosinophilic granules, (n) Cytoplasmatic masses without 
nuclei. 

Fig. 3. — Cervical lymph-glands of the fowl ; normal and leuksemic. Actual 
size and X 2. Note the great increase in size; replacement of fat by the 
greatly swollen parenchymatous lobules. 

Fig. 4. — Normal fowl with organs in situ. Weight, 1750 gm. Note the 
well-nourished condition of the body; the abundance of fat, subcutaneously, 



34 Harry C. Schmeisser. 

in the neck, and in the omentum; the large muscles; size of heart and 
liver. 

Pig. 5. — Leukaemic fowl with organs in situ. Weight, 1350 gm. Note 
great emaciation of body; almost entire absence of fat; atrophy of muscles; 
large heart; enormous liver with the characteristic myeloid infiltrations. 

Fig. 6. — Spleen of the fowl; normal and leukaemic, actual size; surface 
and section. Note the enormous increase in size; in upper half of surface, 
circumscribed areas of myeloid infiltration; the swollen pulp and infiltra 
tions on section. 



DESCRIPTION OF PLATE I. 

Fig. 1. — Normal blood of the fowl. Wilson's stain. Zeiss objective 1/12, 
eye-piece No. 3. Composite picture, (a) Normocytes, (b) Blood platelets, 
(c) Polymorphonuclear leucocyte with eosinophilic rods, {d) Polymor- 
phonuclear leucocyte with eosinophilic granules, (e. e) Lymphocytes 
(small and large). (/) Large mononuclear cell, {g) Mast cell. 

Fig. 2. — Leuksemic blood of the fowl. Wilson's stain. Zeiss objective 
1/12, eye-piece No. 3. Composite picture, (a) Normal normocytes, (b) 
Normocytes showing anisocytosis, poikilocytosis, polychromatophilia, with 
swelling of nucleus and separation of its chromatin, (c) Normoblast. 
id) Megaloblast. (e) Mitoses of erythrocytes, all stages from monaster 
to complete division of nucleus. (/) Blood platelets; both cell and nucleus 
increased in size; increase in size with two nuclei, ig) Polymorphonu- 
clear leucocyte with eosinophilic rods, (h) Polymorphonuclear leucocyte 
with eosinophilic granules. (i) Lymphocyte. ij) Large mononuclear 
cell; same size and larger than normal with both nucleus and cytoplasm 
paler, (fc) Mitoses of large mononuclear cell; all stages, from monaster 
to complete separation of nucleus. (l) Mast cell. (m) Mononuclear 
myelocyte with eosinophilic granules, (n) Cytoplasmatic masses without 
nuclei. 



THE JOHNS HOPKINS HOSPITAL REPORTS. 



PLATE I. 




Fig. 1. 



J- % 






m ^ 



SULf 



(^ 



^ % 



S 






J 




# ♦ 






n 

•< 













% 



Fig. 2. 



Dorothea Pennington fee. 



THE JOHNS HOPKINS HOSPITAL REPORTS. 



PLATE M. 





NoTTnaT^gland-s 





Actual size. 



LeuKaemic gland 
x2. 



Fig. 3. — Cervical lymphglands of the fowl: nor- 
mal and leuksemic. Actual size and X 2. Note 
the great increase in size; replacement of fat by 
the greatly swollen parenchymatous lobules. 




Joniial spleen 

actual size 



Surface 



• 



Section 



Leukaetnic spleen 

actual size 



Surface 



Section 




Fig. 6. — Spleen of the fowl; normal and leukaemic, actual 
size; surface and section. Note the enormous increase in 
size; in upper half of surface circumscribed areas of myeloid 
infiltration; the swollen pulp and infiltrations on section. 



THE JOHNS HOPKINS HOSPITAL REPORTS. 



PLATE III. 




Fig. 4. — Normal fowl with organs in situ. Weight, 1750 gm. Note the 
well-nourished condition of the body: the abundance of fat, subcutaneously, 
in the neck, and in the omentum; the large muscles; size of heart and liver. 



THE JOHNS HOPKINS HOSPITAL REPORTS. 



PLATE IV. 




Fig. 5. — Leuksemic fowl with organs in situ. Weight, 1350 gm. Note great 
emaciation of body; almost entire absence of fat; atrophy of muscles; large 
heart; and enormous liver with the characteristic myeloid infiltrations. 



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